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Protein

GDNF family receptor alpha-3

Gene

GFRA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for the glial cell line-derived neurotrophic factor, ARTN (artemin). Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase.1 Publication

GO - Molecular functioni

  • axon guidance receptor activity Source: Ensembl
  • receptor binding Source: ProtInc

GO - Biological processi

  • nervous system development Source: ProtInc
  • neuron migration Source: Ensembl
  • peripheral nervous system development Source: ProtInc
  • signal transduction Source: ProtInc
  • sympathetic nervous system development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
GDNF family receptor alpha-3
Short name:
GDNF receptor alpha-3
Short name:
GDNFR-alpha-3
Short name:
GFR-alpha-3
Gene namesi
Name:GFRA3
ORF Names:UNQ339/PRO538/PRO3664
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:4245. GFRA3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28655.

Polymorphism and mutation databases

BioMutaiGFRA3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 31311 PublicationAdd
BLAST
Chaini32 – 374343GDNF family receptor alpha-3PRO_0000010789Add
BLAST
Propeptidei375 – 40026Removed in mature formSequence AnalysisPRO_0000010790Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi95 – 951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi148 – 1481N-linked (GlcNAc...)Sequence Analysis
Glycosylationi309 – 3091N-linked (GlcNAc...)1 Publication
Lipidationi374 – 3741GPI-anchor amidated asparagineSequence Analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiO60609.
PRIDEiO60609.

PTM databases

PhosphoSiteiO60609.

Expressioni

Tissue specificityi

Widely expressed in adult and fetus which exhibit a similar pattern. Essentially not expressed in the central nervous system, but highly expressed in several sensory and sympathetic ganglia of the peripheral nervous system. Moderate expression in many non-neuronal tissues, particularly those of the digestive and urogenital systems, but high expression in stomach and appendix. Several types of glandular tissues show low expression. Very low or no expression detected in the hematopoietic system.1 Publication

Gene expression databases

BgeeiO60609.
CleanExiHS_GFRA3.
ExpressionAtlasiO60609. baseline and differential.
GenevisibleiO60609. HS.

Organism-specific databases

HPAiHPA020731.

Interactioni

Protein-protein interaction databases

BioGridi108944. 1 interaction.
DIPiDIP-29114N.
STRINGi9606.ENSP00000274721.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi161 – 17010Combined sources
Helixi173 – 18513Combined sources
Turni188 – 1903Combined sources
Helixi193 – 20614Combined sources
Helixi209 – 2168Combined sources
Helixi225 – 2339Combined sources
Helixi237 – 2404Combined sources
Helixi248 – 2569Combined sources
Helixi259 – 27113Combined sources
Beta strandi274 – 2763Combined sources
Beta strandi281 – 2833Combined sources
Helixi285 – 2939Combined sources
Turni294 – 2974Combined sources
Beta strandi302 – 3043Combined sources
Beta strandi307 – 3093Combined sources
Beta strandi312 – 3154Combined sources
Helixi322 – 3243Combined sources
Helixi325 – 33612Combined sources
Helixi339 – 35517Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2GH0X-ray1.92A/B151-363[»]
ProteinModelPortaliO60609.
SMRiO60609. Positions 44-357.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60609.

Family & Domainsi

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG83952.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000059598.
HOVERGENiHBG051726.
InParanoidiO60609.
OMAiCHRRMKH.
OrthoDBiEOG7FBRJ3.
PhylomeDBiO60609.
TreeFamiTF331647.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003505. GDNF_rcpt_A3.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PRINTSiPR01319. GDNFRALPHA3.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60609-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVRPLNPRPL PPVVLMLLLL LPPSPLPLAA GDPLPTESRL MNSCLQARRK
60 70 80 90 100
CQADPTCSAA YHHLDSCTSS ISTPLPSEEP SVPADCLEAA QQLRNSSLIG
110 120 130 140 150
CMCHRRMKNQ VACLDIYWTV HRARSLGNYE LDVSPYEDTV TSKPWKMNLS
160 170 180 190 200
KLNMLKPDSD LCLKFAMLCT LNDKCDRLRK AYGEACSGPH CQRHVCLRQL
210 220 230 240 250
LTFFEKAAEP HAQGLLLCPC APNDRGCGER RRNTIAPNCA LPPVAPNCLE
260 270 280 290 300
LRRLCFSDPL CRSRLVDFQT HCHPMDILGT CATEQSRCLR AYLGLIGTAM
310 320 330 340 350
TPNFVSNVNT SVALSCTCRG SGNLQEECEM LEGFFSHNPC LTEAIAAKMR
360 370 380 390 400
FHSQLFSQDW PHPTFAVMAH QNENPAVRPQ PWVPSLFSCT LPLILLLSLW
Length:400
Mass (Da):44,511
Last modified:July 19, 2004 - v2
Checksum:iB0BC252FE1F072C7
GO
Isoform 2 (identifier: O60609-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-157: Missing.

Show »
Length:369
Mass (Da):40,930
Checksum:i43DEAB2E6B900CE3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081K → R in AAC24355 (PubMed:9576965).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei127 – 15731Missing in isoform 2. 2 PublicationsVSP_010942Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF051767 mRNA. Translation: AAC24355.1.
AY358997 mRNA. Translation: AAQ89356.1.
AY359037 mRNA. Translation: AAQ89396.1.
AK297693 mRNA. Translation: BAG60051.1.
AK314022 mRNA. Translation: BAG36733.1.
CH471062 Genomic DNA. Translation: EAW62152.1.
CH471062 Genomic DNA. Translation: EAW62153.1.
BC037951 mRNA. Translation: AAH37951.1.
CCDSiCCDS4201.1. [O60609-1]
RefSeqiNP_001487.2. NM_001496.3. [O60609-1]
UniGeneiHs.58042.

Genome annotation databases

EnsembliENST00000274721; ENSP00000274721; ENSG00000146013.
GeneIDi2676.
KEGGihsa:2676.
UCSCiuc003lcn.3. human. [O60609-1]
uc003lco.3. human. [O60609-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF051767 mRNA. Translation: AAC24355.1.
AY358997 mRNA. Translation: AAQ89356.1.
AY359037 mRNA. Translation: AAQ89396.1.
AK297693 mRNA. Translation: BAG60051.1.
AK314022 mRNA. Translation: BAG36733.1.
CH471062 Genomic DNA. Translation: EAW62152.1.
CH471062 Genomic DNA. Translation: EAW62153.1.
BC037951 mRNA. Translation: AAH37951.1.
CCDSiCCDS4201.1. [O60609-1]
RefSeqiNP_001487.2. NM_001496.3. [O60609-1]
UniGeneiHs.58042.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2GH0X-ray1.92A/B151-363[»]
ProteinModelPortaliO60609.
SMRiO60609. Positions 44-357.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108944. 1 interaction.
DIPiDIP-29114N.
STRINGi9606.ENSP00000274721.

PTM databases

PhosphoSiteiO60609.

Polymorphism and mutation databases

BioMutaiGFRA3.

Proteomic databases

PaxDbiO60609.
PRIDEiO60609.

Protocols and materials databases

DNASUi2676.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274721; ENSP00000274721; ENSG00000146013.
GeneIDi2676.
KEGGihsa:2676.
UCSCiuc003lcn.3. human. [O60609-1]
uc003lco.3. human. [O60609-2]

Organism-specific databases

CTDi2676.
GeneCardsiGC05M137588.
HGNCiHGNC:4245. GFRA3.
HPAiHPA020731.
MIMi605710. gene.
neXtProtiNX_O60609.
PharmGKBiPA28655.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG83952.
GeneTreeiENSGT00550000074579.
HOGENOMiHOG000059598.
HOVERGENiHBG051726.
InParanoidiO60609.
OMAiCHRRMKH.
OrthoDBiEOG7FBRJ3.
PhylomeDBiO60609.
TreeFamiTF331647.

Miscellaneous databases

EvolutionaryTraceiO60609.
GeneWikiiGFRA3.
GenomeRNAii2676.
NextBioi10566.
PROiO60609.
SOURCEiSearch...

Gene expression databases

BgeeiO60609.
CleanExiHS_GFRA3.
ExpressionAtlasiO60609. baseline and differential.
GenevisibleiO60609. HS.

Family and domain databases

InterProiIPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003505. GDNF_rcpt_A3.
[Graphical view]
PfamiPF02351. GDNF. 3 hits.
[Graphical view]
PRINTSiPR01319. GDNFRALPHA3.
PR01316. GDNFRECEPTOR.
SMARTiSM00907. GDNF. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Lung and Substantia nigra.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Pancreas.
  6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 32-46.
  7. "Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex."
    Baloh R.H., Tansey M.G., Lampe P.A., Fahrner T.J., Enomoto H., Simburger K.S., Leitner M.L., Araki T., Johnson E.M. Jr., Milbrandt J.
    Neuron 21:1291-1302(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors."
    Wang X., Baloh R.H., Milbrandt J., Garcia K.C.
    Structure 14:1083-1092(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 151-363 IN COMPLEX WITH ARTN, GLYCOSYLATION AT ASN-309.

Entry informationi

Entry nameiGFRA3_HUMAN
AccessioniPrimary (citable) accession number: O60609
Secondary accession number(s): B2RA36
, B4DMY9, Q6UW20, Q8IUZ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: July 19, 2004
Last modified: July 22, 2015
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.